• Carbon ion
• Clinical outcomes
• Locoregional recurrence
• Malignancy
• Reirradiation
• Toxicities

• Hadrontherapy
• Radio-induced secondary tumor
• Radioresistant tumor
• Rare tumor
• Recurrent tumor

• Carbon ions
• Particle therapy
• Protons
• Synchrotron based facilities

• Bundesministerium für Bildung und Forschung
• HORIZON EUROPE European Research Council
• Technische Hochschule Mittelhessen (3418)

• Breast cancer
• artificial intelligence
• image guided radiation therapy
• radiomics
• technology

• Humans
• Female
• Breast Neoplasms/radiotherapy
• Artificial Intelligence
• Radiotherapy, Image-Guided/methods
• Magnetic Resonance Imaging/methods

• Carbon-ion radiotherapy (CIRT)
• radiation-induced malignancy
• sarcoma

• H2AX
• N6-methyladenosine
• carbon-ion radiotherapy
• methyltransferase-like 3
• non-small-cell lung cancer

• Guidelines
• Hypofractionated radiation
• Non-small cell lung cancer
• Oligometastasis
• Radiotherapy
• Stereotactic radiation therapy

Radiation therapy is part of recommendations in the adjuvant settings for advanced stage or as exclusive treatment in unresectable thymic epithelial tumors (TETs). However, first-generation techniques delivered substantial radiation doses to critical organs at risk (OARs), such as the heart or the lungs, resulting in noticeable radiation-induced toxicity. Treatment techniques have significantly evolved for TET irradiation, and modern techniques efficiently spare normal surrounding tissues without negative impact on tumor coverage and consequently local control or patient survival. Considering its dosimetric advantages, hadrontherapy (which includes proton therapy and carbon ion therapy) has proved to be worthwhile for TET irradiation in particular for challenging clinical situations such as cardiac tumoral involvement. However, clinical experience for hadrontherapy is still limited and mainly relies on small-size proton therapy studies. This critical review aims to analyze the current status of hadrontherapy for TET irradiation to implement it at a larger scale.

• carbon ion therapy
• hadrontherapy
• proton therapy
• thymic carcinoma
• thymoma

• 3D conformal radiotherapy
• Carbon ion radiotherapy
• Lung metastases
• Proton therapy
• Re-irradiation
• Recurrent lung cancer
• Stereotactic body radiotherapy
• Toxicity

Despite the effectiveness of carbon ion radiotherapy (CIRT) for locally advanced unresectable pancreatic cancer (URPC), isolated local recurrence after CIRT is a therapeutic challenge. Herein, we aimed to evaluate the feasibility and safety of a second course of CIRT for locally recurrent URPC in 10 patients. One patient developed grade 3 diarrhea immediately after the second CIRT; no other grade 3 or higher adverse events were induced by CIRT. The estimated 1-year overall survival rate and local control rate after the second CIRT were 48% and 67%, respectively. Repeated CIRT is feasible with acceptable toxicity for selected patients with locally advanced URPC after CIRT.

Purpose: The feasibility and safety of re-irradiation with carbon ion beams for locally recurrent unresectable pancreatic cancer (URPC) after carbon ion radiotherapy (CIRT) was evaluated. Methods: Medical records from patients with re-irradiated URPC who were treated with CIRT between November 2017 and February 2019 were reviewed. Inclusion criteria were (1) isolated local recurrence after CIRT, (2) URPC, and (3) tumor located at least 3 mm from the gastrointestinal tract. The first and second CIRT irradiation doses were 55.2 Gy (relative biological effectiveness) in 12 fractions. Results: Ten patients met the inclusion criteria. The median follow-up period was 25.5 months (range, 16.0–69.1) after the first CIRT and 8.9 months (range, 6.4–18.9) after the second CIRT. The median interval between the initial CIRT and the local recurrence was 15.8 months (range, 8.0–50.1). One patient developed grade 3 diarrhea immediately after the second CIRT; no other grade 3 or higher adverse events were attributed to CIRT. The estimated 1-year overall survival, local control, and progression-free survival rates after the second CIRT were 48%, 67%, and 34%, respectively. Conclusion: Repeated CIRT is feasible with acceptable toxicity for selected patients with locally advanced URPC after CIRT.

• carbon ion radiotherapy
• local recurrence
• locally advanced pancreatic cancer
• pancreatic cancer
• re-irradiation

• Locoregional relapse
• Particle therapy
• Reirradiation
• Stereotactic body radiotherapy
• Survival outcome
• Toxicity

• Breast
• Hadron
• Heavy
• Particle
• Tumor

• carbon-ion radiotherapy
• lymph node metastasis
• non-small cell lung cancer
• particle beam therapy
• postoperative recurrence

The efficacy and safety of carbon‐ion radiotherapy (CIRT) for locally advanced non‐small‐cell lung cancer (LA‐NSCLC) remain unclear. We reported the clinical outcomes of CIRT for LA‐NSCLC. Data for 141 eligible patients who received CIRT between 1995 and 2015 were retrospectively analyzed. Local control (LC), locoregional control (LRC), progression‐free survival (PFS) and overall survival (OS) were calculated using the Kaplan‐Meier method. The median age was 75.0 years. Overall, 21 (14.9%), 57 (40.4%), 43 (30.5%) and 20 (14.2%) patients had T1, T2, T3 and T4 disease, respectively. Moreover, 51 (36.2%), 45 (31.9%), 40 (28.4%) and 5 (3.5%) patients had N0, N1, N2 and N3 disease, respectively. Furthermore, 34 (24.1%), 42 (29.8%), 45 (31.9%) and 20 (14.2%) patients had stages IIA, IIB, IIIA and ΙΙΙB disease, respectively. Overall, 62 (44.0%), 60 (42.6%), 8 (5.7%) and 11 (7.8%) patients had adenocarcinoma, squamous cell carcinoma, large cell carcinoma, and others, respectively. The median dose was 72.0 Gy (relative biological effectiveness). No patient received concurrent chemotherapy. Median follow‐up periods were 29.3 (1.6‐207.7) and 40.0 (10.7‐207.7) months for all patients and survivors, respectively. Two‐year LC, PFS and OS rates were 80.3%, 40.2% and 58.7%, respectively. Overall, 1 (0.7%), 5 (3.5%) and 1 (0.7%) patient developed Grades 4 (mediastinal hemorrhage), 3 (radiation pneumonitis) and 3 (bronchial fistula) toxicities, respectively. Multivariate analysis showed adenocarcinoma and N2/3 classification as significant poor prognosticators of PFS. CIRT is an effective treatment with acceptable toxicity for LA‐NSCLC, especially for elderly patients or patients with severe comorbidities who cannot be treated with surgery or chemoradiotherapy.

• carbon-ion radiotherapy
• effectiveness
• elderly patients
• locally advanced non-small-cell lung cancer
• radiation therapy

Intrathoracic recurrence after carbon‐ion radiotherapy for primary or metastatic lung tumors remains a major cause of cancer‐related deaths. However, treatment options are limited. Herein, we report on the toxicity and efficacy of re‐irradiation with carbon‐ion radiotherapy for locoregionally recurrent, metastatic, or secondary lung tumors. Data of 95 patients with prior intrathoracic carbon‐ion radiotherapy who were treated with re‐irradiation with carbon‐ion radiotherapy at our institution between 2006 and 2016 were retrospectively analyzed. Seventy‐three patients (76.8%) had primary lung tumors and 22 patients (23.2%) had metastatic lung tumors. The median dose of initial carbon‐ion radiotherapy was 52.8 Gy (relative biological effectiveness) and the median dose of re‐irradiation was 66.0 Gy (relative biological effectiveness). None of the patients received concurrent chemotherapy. The median follow‐up period after re‐irradiation was 18 months. In terms of grade ≥3 toxicities, one patient experienced each of the following: grade 5 bronchopleural fistula, grade 4 radiation pneumonitis, grade 3 chest pain, and grade 3 radiation pneumonitis. The 2‐year local control and overall survival rates were 54.0% and 61.9%, respectively. In conclusion, re‐irradiation with carbon‐ion radiotherapy was associated with relatively low toxicity and moderate efficacy. Re‐irradiation with carbon‐ion radiotherapy might be an effective treatment option for patients with locoregionally recurrent, metastatic, or secondary lung tumors.

• carbon-ion radiotherapy
• lung cancer
• re-irradiation
• recurrence
• toxicity